Non-peptidic cysteine derivatives as inhibitors of matrix metalloproteinases.
By exploiting the thiol function of L-cysteine as a chelating group of the active-site zinc atom of matrix metalloproteinases (MMPs), N- and C-terminal derivatization of this amino acid with aliphatic and aromatic groups allowed us to explore the selectivity of the S and/or S' binding subsites of human neutrophil collagenase (MMP8) and stromelysin (MMP3). With N-benzyloxycarbonyl-L-cysteine-(2-phenyl)ethylamide a submicromolar inhibitor of MMP8 was discovered.
Müller
J C
JC
Max-Planck-Institut für Biochemie, Martinsried, Germany.
von Roedern
E G
EG
Grams
F
F
Nagase
H
H
Moroder
L
L
D003545:Cysteine / Q000031:analogs & derivatives*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020784:Matrix Metalloproteinase 8; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020784:Matrix Metalloproteinase 8; D003545:Cysteine